Open AccessActivation of Escherichia coli prohemolysin to the membrane‐targetted toxin by HlyC‐directed ACP‐dependent fatty acylation *
Author(s) -
Hughes Colin,
Issartel JeanPaul,
Hardie Kim,
Stanley Peter,
Koronakis Eva,
Koronakis Vassilis
Publication year - 1992
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1111/j.1574-6968.1992.tb05884.x
Subject(s) - escherichia coli , activator (genetics) , moiety , chemistry , biochemistry , acylation , fatty acid , acyl carrier protein , bacteria , toxin , in vitro , biology , stereochemistry , receptor , gene , genetics , catalysis
Hemolysin (HlyA) and related toxins of Escherichia coli and other Gram‐negative pathogenic bacteria form membrane pores in cells of the host immune system, causing cell dysfunction and death. An insight into the mechanism by which HlyA is targetted to mammalian cell membranes was achieved by establishing in vitro activation of the non‐toxic precursor proHlyA. By this approach we have discovered that conversion of proHlyA to the post‐translational active HlyA toxin is determined by fatty acylation of proHlyA in an apparently novel process directed by the HlyC homodimer activator protein, and dependent upon the cellular acyl carrier protein (ACP). By further exploiting the in vitro activation system it is now possible to obtain direct evidence that HlyC binds to an internal recognition sequence in the proHlyA precursor, in this way providing specificity for the transfer to proHlyA of a fatty acid moiety carried by the ACP. It is possible that the fatty acid modification determines directly the binding of HlyA to mammalian membrane lipids, thus initiating the toxin interaction with the target cells.